One-Week Exposure to a Free-Choice High-Fat High-Sugar Diet Does Not Interfere With the Lipopolysaccharide-Induced Acute Phase Response in the Hypothalamus of Male Rats

Abstract

Obesity has been associated with increased susceptibility to infection in humans and rodents. Obesity is also associated with low-grade hypothalamic inflammation that depends not only on body weight but also on diet. In the present study, we investigated if the bacterial endotoxin [lipopolysaccharide (LPS)]-induced acute phase response is aggravated in rats on a 1-week free-choice high-fat high-sugar (fcHFHS) diet and explained by diet-induced hypothalamic inflammation. Male Wistar rats were on an fcHFHS diet or chow for 1 week and afterwards intraperitoneally injected with LPS or saline. Hypothalamic inflammatory intermediates and plasma cytokines were measured after LPS. Both LPS and the fcHFHS diet altered hypothalamic Nfkbia mRNA and nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha (NFKBIA) protein levels, whereas Il1β, Il6, and Tnfα mRNA expression was solely induced upon LPS. We observed an interaction in hypothalamic Nfkbia and suppressor of cytokine signaling (SOCS) 3 mRNA upon LPS; both were higher in rats on a fcHFHS diet compared with chow animals. Despite this, plasma cytokine levels between fcHFHS diet-fed and chow-fed rats were similar after LPS administration. Consuming a fcHFHS diet but not LPS injections increased hypothalamic Atf4 (a cellular stress marker) mRNA expression, whereas Tlr4 mRNA was decreased only upon LPS. Our study does not support a role for diet-induced mild hypothalamic inflammation in the increased susceptibility to infection despite altered Nfkbia and Socs3 mRNA expression after the diet. Additional factors, related to increased fat mass, might be involved.

Simvastatin ameliorates oxidative stress levels in HepG2 cells and hyperlipidemic rats

“…Thus, the findings were validated through in-vitro analysis in LPS induced oxidative stress in HepG2 cells and HFD induced oxidative stress in hyperlipidemic rats. Various studies show that the bacterial endotoxins, LPS as one of the compounds capable of inducing oxidative stress in different cells of different organs and lead to the production of toxins ( Belegri et al., 2018 ). LPS causes the accumulation of ROS resulting in cell cytotoxicity.…”

“…Besides all these, there are counter processes or different reactions in order to balance the effect of oxidative stress. Thus, catalase, peroxides, and SOD are considered as indexes to assess the level of oxidative stress in HepG2 cells ( Kaplan et al., 2021 ; Belegri et al., 2018 ). Thus, we investigated the role of simvastatin at a concentration of 10 ​μM as per the reported literature ( Bak et al., 2012 ; Lasker et al., 2019 ) for the amelioration of LPS induced oxidative stress.…”

Correlation between Salivary Lipopolysaccharide ofPorphyromonas gingivaliswith Circulatory Immunoglobulin-E and Immunoglobulin-G4in Periodontally Healthy Children with House Dust Mite Allergy

“…As a unique endotoxin, lipopolysaccharide-driven inflammatory responses can induce a more pronounced pro-inflammatory cytokine response [28]. At very low concentration, lipopolysaccharide may induce atopic inflammatory responses by Th-1 shifting into Th-2, which is more potent to stimulate antibodies production [29].…”

Immunology of gut microbiome and liver in non-alcoholic fatty liver disease (NAFLD): mechanisms, bacteria, and novel therapeutic targets

“…As we already mentioned TLR4 signalling is involved in the inflammatory response and also induces metabolic disturbances promoting further liver damage in patients with NAFLD. [55,56] Although there are many other TLRs that can recognize other bacterial components (e.g., TLR2, TLR5, and TLR9) [57,58], their particular contribution to NASH development is poorly defined now. Picture 1 summarizes the various TLRs mechanisms involved in NAFLD pathogenesis.…”